The goal of this grant is to evaluate the role of apoprotein genetic variation and metabolism in determining and individual's atherosclerosis susceptibility and response to saturated fat and cholesterol in the diet. Three projects are proposed: 1) A clinical investigation study in humans to examine the effect of dietary fat in apo E synthesis and catabolism in the monocyte-macrophage. This project will assess whether diet can alter apo E metabolism in a cell type thought to play an important part in atherogenesis through its role in the reverse cholesterol transport pathway. 2) A nutritional study in two species of monkeys, one known to have high HDL levels and atherosclerosis resistance and the other low HDL levels and atherosclerosis sensitivity, of dietary fat effects on the synthesis of most of the apoproteins. This project will provide the first comprehensive understanding of diet effects on apoprotein synthesis in nonhuman primates and may reveal correlations between parameters of diet responsiveness and/or atherosclerosis susceptibility and apoprotein synthetic rates. 3) A clinical study to determine whether DNA polymorphisms associated with the apoprotein genes predict atherosclerosis susceptibility and/or diet response. This study should reveal genetic markers associated with atherosclerosis susceptibility, the expression of type III HLP, and lipoprotein and cholesterol balance parameters associated with dietary response. It is our hope that these investigations will lay the foundation for a new field of nutritional genetics at the molecular level.